This proposal builds on the enzyme chemical and technical knowledge we have accumulated over the past years regarding the role of Factor XIII in blood clotting, and it is oriented towards studying molecular defects of fibrin stabilization in patients. Malfunctioning of the fibrin stabilizing factor system often leads to severe hemorrhaging, and a number of unique cases are under analysis. In addition, we propose to improve and automate Factor XIII assays for testing large numbers of human plasma samples in order to weigh fluctuations of activity of this factor in health and disease. Activity data will be matched against the immunological testing of Factor XIII proteins (a and b subunits). A comprehensive approach aimed at standardizing purified Factor XIII zymogen preparations will be explored for therapeutic purposes.